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Diphenhydramine / guaifenesin Side Effects

Applies to diphenhydramine/guaifenesin: oral liquid.

Cardiovascular

Cardiovascular side effects of diphenhydramine have included hypotension, tachycardia, and palpitations.[Ref]

Gastrointestinal

Gastrointestinal side effects of diphenhydramine have been usually mild and included nausea and dry mouth. Gastrointestinal side effects of guaifenesin have included stomach upset and vomiting with higher than recommended doses. Doses recommended for expectoration have rarely been associated with gastrointestinal upset.[Ref]

Genitourinary

Genitourinary side effects have included urinary retention and dysuria as a result of the anticholinergic effects of diphenhydramine.[Ref]

Hematologic

Hematologic side effects such as hemolytic anemia, thrombocytopenia, and agranulocytosis have been rarely caused by antihistamines.[Ref]

Hypersensitivity

Most commonly, diphenhydramine hypersensitivity has manifested itself in patients receiving systemic drug after being sensitized to it by topical application. Sensitization with systemic administration has also been reported.[Ref]

Hypersensitivity side effects of diphenhydramine have included rash, pruritus and eczema. Photosensitivity reactions have also been reported.[Ref]

Nervous system

Nervous system side effects of diphenhydramine have included depression with drowsiness and sedation in nearly all patients treated. Motor skills may be impaired. Dystonic reactions have been reported after single doses of diphenhydramine. Nervous system side effects of guaifenesin have occasionally included dizziness and headache.[Ref]

The CNS depressant effect of diphenhydramine parallels its plasma concentrations. The plasma concentration threshold for sedation is 30 to 42 ng/mL, and to cause mental impairment is 58 to 74 ng/mL. Patients should be warned against driving while taking diphenhydramine.

Dystonic reactions have been accompanied by dizziness, mental confusion, rigidity, lip and tongue protrusion, trismus, torticollis, and swallowing difficulties and generally resolve spontaneously. Toxic encephalopathy has been reported in a child with chicken pox treated generously with topical diphenhydramine.

Delirium has been reported in elderly patients with mild dementia following a small oral dose of diphenhydramine[Ref]

Ocular

Ocular side effects of diphenhydramine have included blurred vision, diplopia, and dry eyes due to anticholinergic effects.[Ref]

Dermatologic

Dermatologic side effects of guaifenesin have included rare reports of rash.[Ref]

References

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2. Product Information. Benadryl (diphenhydramine). Parke-Davis. 2002;PROD.

3. Covington TR, eds., Lawson LC, Young LL. Handbook of Nonprescription Drugs. Washington, DC: American Pharmaceutical Association. 1993.

4. Horio T. Allergic and photoallergic dermatitis from diphenhydramine. Arch Dermatol. 1976;112:1124-6.

5. Emmett EA. Diphenhydramine photoallergy. Arch Dermatol. 1974;110:249-52.

6. Davenport PM, Wilhelm RE. An unusual vasculitis due to diphenhydramine. Cutaneous and central nervous system involvement. Arch Dermatol. 1965;92:577-80.

7. Coskey RJ. Contact dermatitis caused by diphenhydramine hydrochloride. J Am Acad Dermatol. 1983;8:204-6.

8. Lawrence CM, Byrne JP. Eczematous eruption from oral diphenhydramine. Contact Dermatitis. 1981;7:276-7.

9. Heine A. Diphenhydramine: a forgotten allergen? Contact Dermatitis. 1996;35:311-2.

10. Yamada S, Tanaka M, Kawahara Y, Inada M, Ohata Y. Photoallergic contact dermatitis due to diphenhydramine hydrochloride. Contact Dermatitis. 1998;38:282.

11. Barranco P, LopezSerrano MC, MorenoAncillo A. Anaphylactic reaction due to diphenhydramine. Allergy. 1998;53:814.

12. Lavenstein BL, Cantor FK. Acute dystonia: an unusual reaction to diphenhydramine. JAMA. 1976;236:291.

13. Carruthers SG, Shoeman DW, Hignite CE, Azarnoff DL. Correlation between plasma diphenhydramine level and sedative and antihistamine effects. Clin Pharmacol Ther. 1978;23:375-82.

14. Gengo F, Gabos C, Miller JK. The pharmacodynamics of diphenhydramine-induced drowsiness and changes in mental performance. Clin Pharmacol Ther. 1989;45:15-21.

15. Burns M, Moskowitz H. Effects of diphenhydramine and alcohol on skills performance. Eur J Clin Pharmacol. 1980;17:259-66.

16. Roila F, Donati D, Basurto C, Del Favero A. Diphenhydramine and acute dystonia . Ann Intern Med. 1989;111:92-3.

17. Filloux F. Toxic encephalopathy caused by topically applied diphenhydramine. J Pediatr. 1986;108:1018-20.

18. Brait KA, Zagerman AJ. Dyskinesias after antihistamine use . N Engl J Med. 1977;296:111.

19. Jones B, Lal S. Tardive dyskinesia uncovered after ingestion of Sominex, an over-the- counter drug. Can J Psychiatry. 1985;30:370-1.

20. Santora J, Rozek S, Samie MR. Diphenhydramine-induced dystonia . Clin Pharm. 1989;8:471.

21. Borbely AA, Youmbi-Balderer G. Effect of diphenhydramine on subjective sleep parameters and on motor activity during bedtime. Int J Clin Pharmacol Ther Toxicol. 1988;26:392-6.

22. Tejera CA, Saravay SM, Goldman E, Gluck L. Diphenhydramine-induced delirium in elderly hospitalized patients with mild dementia. Psychosomatics. 1994;35:399-402.

23. Etzel JV. Diphenhydramine-induced acute dystonia. Pharmacotherapy. 1994;14:492-6.

24. Product Information. Robitussin (guaifenesin). Wyeth-Ayerst Laboratories. 2001;PROD.

25. Ramaekers JG, Ohanlon JF. Acrivastine, terfenadine and diphenhydramine effects on driving performance as a function of dose and time after dosing. Eur J Clin Pharmacol. 1994;47:261-6.

26. Vuurman EFPM, Vanveggel LMA, Sanders RL, Muntjewerff ND, Ohanlon JF. Effects of semprex-d and diphenhydramine on learning in young adults with seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 1996;76:247-52.

27. Simons FER, Fraser TG, Reggin JD, Simons KJ. Comparison of the central nervous system effects produced by six h-1-receptor antagonists. Clin Exp Allergy. 1996;26:1092-7.

28. Sexton JD, Pronchik DJ. Diphenhydramine induced psychosis with therapeutic doses. Am J Emerg Med. 1997;15:548-9.

29. Richardson GS, Roehrs TA, Rosenthal L, Koshorek G, Roth T. Tolerance to daytime sedative effects of h1 antihistamines. J Clin Psychopharmacol. 2002;22:511-5.

30. Seedor JA, Lamberts D, Bergmann RB, Perry HD. Filamentary keratitis associated with diphenhydramine hydrochloride (Benadryl). Am J Ophthalmol. 1986;101:376-7.

31. Hopfenbeck JR, Cowley DS, Radant A, Greenblatt DJ, Roybyrne PP. Effects of diphenhydramine on human eye movements. Psychopharmacology (Berl). 1995;118:280-6.

Further information

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Some side effects may not be reported. You may report them to the FDA.

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